Our research objective is to determine the genetic control of antibody structure. The analysis of the amino acid sequence of mouse lambda chains and heavy chains will allow an estimate of the number of germ-line genes coding for the structure of these proteins and will suggest mechanisms by which antibodies are diversified. Genetic analysis of the loci that control the immune response to certain antigens may provide an estimate of the number of heavy chain variable region genes, an understanding of the genetic relationship between variable and constant regions, and by identifying loci linked to heavy chain loci will lead to experimental approaches for the study of the special features of antibody regulation. The primary structure analysis of myeloma antibodies and normal antibodies of restricted heterogeneity with similar specificities is being carried out. These comparisons will demonstrate the effect of amino acid replacements on antibody specificity.